“Cold” colorectal cancer faces a bottleneck in immunotherapy

Liu, Jialiang; Yang, Ming; Bai, Jun-Ge; Liu, Zheng; Wang, Xishan

doi:10.4251/wjgo.v15.i2.240

Cited by 8 publications

(3 citation statements)

References 109 publications

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“…Indeed, in the still normal colonic mucosa, various inflammatory mediators can actively contribute to the creation of a TME favorable to cell transformation, survival and proliferation [87]. The mutual interaction of epithelial cells within the TME influences the stages of tumorigenesis driven to a large extent by inflammation This may be an attractive therapeutic target to control inflammation in the colonic mucosa [88] Furthermore, IEC can drive the plasticity of stromal cells in the TME under the influence of extrinsic factors, such as diet, and microbiota composition contributing to inflammation and tumorigenesis in CRC [87,89] However, understanding the interactions between Wnt signaling and inflammatory/immune responses in tumor onset remains a necessary goal for both prevention and therapy, given that the majority of CRCs appear to be immunologically "cold" tumors unresponsive to therapies with immune checkpoint inhibitors [90].…”

Section: Discussionmentioning

confidence: 99%

The Interplay among Wnt/β-Catenin Family Members in Colorectal Adenomas and Surrounding Tissues

D'Antonio,

Fantini,

Moscatello

et al. 2024

Preprint

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Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

The Interplay among Wnt/β-Catenin Family Members in Colorectal Adenomas and Surrounding Tissues

D'Antonio,

Fantini,

Moscatello

et al. 2024

Preprint

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“…According to IS, CRCs can be classified into hot and cold tumors. Improving the efficacy of immunotherapy is associated with converting cold tumors into hot tumors or T-cell-inflammatory tumors [ 20 ]. In our previous work, we highlighted the significance of TILs [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Implications of Intratumoral Budding in Colorectal Cancer: Detailed Analysis Based on Tumor-Infiltrating Lymphocytes

Pyo,

Choi,

Kim

et al. 2023

JCM

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Background: This study aims to understand the clinical and pathological importance of intratumoral budding (ITB) in colorectal cancer (CRC) and its relationship with tumor-infiltrating lymphocytes (TILs). CRCs can be classified into hot (high immunoscore (IS)) and cold (low IS) tumors. Methods: We investigated the number of ITBs in a hotspot area and categorized them into high-ITB (≥5) and low-ITB (<5) groups. The clinicopathological significance of ITB in human CRCs was evaluated, and a detailed analysis based on tumor-infiltrating lymphocytes (TILs) was also performed. Results: High ITB was identified in 59 of 266 CRC cases (22.2%). High ITB significantly correlated with a poorly differentiated tumor, lympho-vascular invasion, perineural invasion, higher pT stage, lymph node metastasis, and higher metastatic lymph node ratio. High ITB was also significantly correlated with a low IS and low CD8-positive lymphocytic infiltrate. The number of ITBs was substantially higher in the low-IS group than in the high-IS group (3.28 ± 3.31 vs. 2.19 ± 2.59; p = 0.005). High ITB significantly correlated with worse overall survival (p = 0.004). In the low-IS group, CRCs with high ITB had a significantly worse prognosis than those with low ITB (p = 0.021). However, there was no significant difference in prognosis between the high- and low-ITB groups in the high-IS group (p = 0.498). Conclusions: Taken together, high ITB was significantly correlated with aggressive tumor behaviors and worse survival in patients with CRCs. In addition, ITB can be useful for the prognostic stratification of CRCs with low IS.

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“…Among the suggested cancer diagnostic approaches is optical spectroscopy which can measure optical spectra rapidly and noninvasively [16–20]. Here, we propose application of optical spectroscopy in the VIS–NIR spectral region in conjunction with spectrum features analysis.…”

Section: Introductionmentioning

confidence: 99%

Single probe light reflectance spectroscopy and parameter spectrum feature extraction in experimental skin cancer detection and classification

Abookasis

Shemesh

Litwin

et al. 2023

Journal of Biophotonics

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Skin cancer, an anomalous development of skin cells in the epidermis, is among the most common types of cancer worldwide. Because of its clinical importance and to improve early diagnosis and patient management, there is an urgent need to develop noninvasive, accurate medical diagnostic tools. To this aim, light reflectance spectroscopy over the visible and near-infrared spectral range (400-1000 nm) based on a single-fiber six-around-one optical probe was applied to extract nine features used for diagnostics. These features include skewness, entropy, energy, kurtosis, scattering amplitude, and others, and are spread over each of four different spectral signatures, namely, light reflectance, absorbance, scattering profile approximation, and absorption/scattering ratio. Our preliminary studies focused on 11 adult patients with diagnoses of malignant melanoma (n = 4), basal cell carcinoma (n = 5), and squamous cell carcinoma (n = 2) in a variety of locations on the body. Measurements were taken first in vivo before surgery, at the site of the lesion and from healthy skin of the same patient, and ex vivo after surgical excision, where the lesion was rinsed in saline solution and measurements of the reflected light from the "inside" facing plane of the tissue were taken in the same manner. Overall, experimental results demonstrate that by examining a variety of wavebands, features, and statistical metrics, we can detect and distinguish cancer from normal tissue and different cancer subtypes. Nevertheless, discrepancies in results between in vivo and ex vivo tissue were observed and explanations for these discrepancies are discussed.

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“Cold” colorectal cancer faces a bottleneck in immunotherapy

Cited by 8 publications

References 109 publications

The Interplay among Wnt/β-Catenin Family Members in Colorectal Adenomas and Surrounding Tissues

The Interplay among Wnt/β-Catenin Family Members in Colorectal Adenomas and Surrounding Tissues

Prognostic Implications of Intratumoral Budding in Colorectal Cancer: Detailed Analysis Based on Tumor-Infiltrating Lymphocytes

Single probe light reflectance spectroscopy and parameter spectrum feature extraction in experimental skin cancer detection and classification

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